Background:

IC50: 5.0 μM

GW1929 is a nonthiazolidinedione PPARγ agonist. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors with three isoforms: PPARα, PPARγ, and PPARβ/δ. Among these, PPARγ is highly expressed in various brain regions. A growing evidences have suggested that PPARγ play a key role in pathogenesis of cerebral IR injury

In vitro: GW1929 was tested on currents through L-type voltage-dependent calcium channels (VDCC) in freshly isolated smooth muscle cells. Using Ba2+ as the charge carrier through VDCC, the IC50s for GW1929 and pioglitazone were determined to be 5.0 +/- 0.7 and 10.0 +/- 0.8 μM, respectively. GW1929 and pioglitazone were both effective on inhibiting VDCC and relaxing pressurized arteries, indicating the vasodilation of resistance arteries might be explained by the inhibition of calcium entry through VDCC [1].

In vivo: GW1929 treatment attenuated the neurological damage in focal cerebral IR injury significantly. In addition, the neuroprotective effects of GW1929 were found to be associated with significant reduction in the levels of MMP-9, COX-2, iNOS, TNFα and IL-6. Neuroprotective effects of GW1929 related with significant reduction in TUNEL positive cells in IR challenged brain [2].

Clinical trial: N/A

参考文献:
[1] Heppner TJ,Bonev AD,Eckman DM,Gomez MF,Petkov GV,Nelson MT. Novel PPARgamma agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease calcium channel function and myogenic tone in rat mesenteric arteries. Pharmacology.2005 Jan;73(1):15-22.
[2] Kaundal RK,Sharma SS.  Ameliorative effects of GW1929, a nonthiazolidinedione PPARγ agonist, on inflammation and apoptosis in focal cerebral ischemic-reperfusion injury. Curr Neurovasc Res.2011 Aug 1;8(3):236-45.